Rehman Khurram S, Carr Bruce R, Rainey William E
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032, USA.
J Soc Gynecol Investig. 2003 Sep;10(6):372-80. doi: 10.1016/s1071-5576(03)00118-7.
Gene expression clearly underlies the marked structural and functional differences between the human fetal adrenal (HFA) and adult adrenal. We thus measured expression of steroidogenic enzymes and associated cofactors in these tissues.
Real-time reverse transcriptase polymerase chain reaction was used to quantify transcripts encoding steroidogenic enzymes and the cofactors steroidogenic acute regulatory protein (StAR), cytochrome b5 (CYb5), and P450 oxidoreductase (POR).
Cholesterol side-chain cleavage mRNA levels were 1.9-fold higher in the HFA than in the adult adrenal. Compared with a nonsignificant difference in 17alpha-hydroxylase/17,20 lyase mRNA abundance, CYb5 and POR were expressed 2.3-fold and 2.0-fold higher, respectively, in the HFA. Dehydroepiandrosterone (DHEA) sulfotransferase transcript (SULT2A1) was present at 13-fold higher levels in the HFA than the adult. 3beta-Hydroxysteroid dehydrogenase type II (HSD3B2) mRNA was 127-fold higher in the adult adrenal. StAR, 21-hydroxylase, 11beta hydroxylase, and aldosterone synthase mRNA abundance did not differ significantly.
In the HFA, increased mRNA for cholesterol side-chain cleavage reflects high cholesterol utilization for steroidogenesis. Both CYb5 and POR cofactors may up-regulate 17alpha-hydroxylase/17,20 lyase activity and thus DHEA sulfate production in the HFA. High levels of SULT2A1 mRNA reflect high DHEA sulfonation in the HFA and restricted expression in the adult. Lack of HSD3B2 in the HFA facilitates DHEA synthesis. The novel finding of high levels of 21-hydroxylase and 11beta hydroxylase transcripts in the midgestational HFA merits further investigation. Thus different patterns of steroidogenic enzyme and cofactor gene expression might account for some of the phenotypic differences between the fetal and adult adrenal.
基因表达显然是人类胎儿肾上腺（HFA）与成人肾上腺在结构和功能上显著差异的基础。因此，我们测定了这些组织中类固醇生成酶及相关辅因子的表达。
采用实时逆转录聚合酶链反应来定量编码类固醇生成酶及辅因子类固醇生成急性调节蛋白（StAR）、细胞色素b5（CYb5）和P450氧化还原酶（POR）的转录本。
HFA中胆固醇侧链裂解mRNA水平比成人肾上腺高1.9倍。与17α-羟化酶/17,20裂解酶mRNA丰度的无显著差异相比，CYb5和POR在HFA中的表达分别高2.3倍和2.0倍。硫酸脱氢表雄酮（DHEA）硫酸转移酶转录本（SULT2A1）在HFA中的水平比成人高13倍。成人肾上腺中II型3β-羟类固醇脱氢酶（HSD3B2）mRNA高127倍。StAR基因、21-羟化酶基因、11β-羟化酶基因和醛固酮合成酶mRNA丰度无显著差异。
在HFA中，胆固醇侧链裂解mRNA增加反映了类固醇生成中胆固醇的高利用率。CYb5和POR这两种辅因子都可能上调17α-羟化酶/17,20裂解酶活性，从而增加HFA中硫酸脱氢表雄酮的生成。SULT2A1 mRNA的高水平反映了HFA中硫酸脱氢表雄酮的高磺化作用以及在成人中的有限表达。HFA中缺乏HSD3B2有助于硫酸脱氢表雄酮的合成。妊娠中期HFA中高水平的21-羟化酶和11β-羟化酶转录本这一新发现值得进一步研究。因此，类固醇生成酶和辅因子基因表达的不同模式可能是胎儿和成人肾上腺表型差异的部分原因。
